Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.3.1.28 (chloramphenicol acetyltransferase)
 5,100 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human pregnancy-specific glycoproteins (PSGs) are a family of closely related placental proteins that, together with the carcinoembryonic antigen members, comprise a subfamily within the immunoglobulin superfamily. To facilitate study of the control of PSG expression, we immortalized human placental cell lines with adenovirus-origin-minus (ori-)-simian virus-40 (SV40) recombinant viruses containing either wild-type or temperature-sensitive (ts) A mutants of SV40. Cells transformed with the SV40 tsA chimera (HP-A1 and HP-A2), but not the SV40 wild-type chimera (HP-W1), were temperature sensitive for transformation. All three cell lines expressed trophoblast-specific genes, including PSG and the alpha- and beta-subunits of hCG. Human CG alpha expression was greatly stimulated by (Bu)2cAMP in all three cell lines; shifting HP-A1 and HP-A2 cells to the nonpermissive temperature (39.5 C) further increased hCG alpha expression. At both 33 C (permissive temperature) and 39.5 C, the transformed placental cells expressed PSG mRNAs of 2.2 and 1.7 kilobases; expression was greatly stimulated by sodium butyrate. In the absence of an inducer, the three placental lines synthesized a PSG of 64 kilodaltons (kDa). In the presence of butyrate, they synthesized PSGs of 72, 64, and 54 kDa, similar to the placental PSGs. However, in placenta the predominant species is the 72-kDa product. At 39.5 C, butyrate selectively increased synthesis of the 72-kDa PSG in HP-A1 and HP-A2 cells. To characterize PSG promoter activity, we constructed chloramphenicol acetyltransferase (CAT) fusion genes containing -809 to -44 basepairs up-stream of the translational start site of the PSG6 gene. Using transient expression assays, we demonstrated that the -809/-44 region of the PSG6 gene contained cis-acting sequences that can direct CAT expression in human placental cells. Sodium butyrate, which stimulates PSG expression, greatly increased CAT activity, indicating that butyrate-induced PSG expression is regulated primarily at the level of gene transcription.
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PMID:Immortalization of virus-free human placental cells that express tissue-specific functions. 131 3

The pregnancy-specific glycoproteins (PSGs) of the human placenta and the carcinoembryonic antigens comprise a subfamily within the immunoglobulin superfamily. There may be as many as 20 different PSG genes which are predominantly expressed in the placenta. As an initial step toward understanding the control of PSG expression, we isolated and characterized two nearly identical PSG genes, PSG1 and PSG1-I. PSG1, which lacks exon 1 (5'/L), but contains exons 2 (L/N), 3 (A1), 4 (A2), and 5 (B2-C), encodes five previously identified type I transcripts, PSG1a, 1b, 1c, 1d, and 1e in a L/N-A1-A2-B2-C domain arrangement. PSG1-I, which contains a complete transcriptional unit consisting of exons 5'/L, L/N, A1, and B2-C, encodes type II PSG transcripts in a L/N-A1-B2-C domain arrangement. The predicted PSG1-I-encoded proteins share nearly complete sequence identity with the PSG1-encoded members, except the latter contain extra A domains. Amplification by polymerase chain reaction of placental or hydatidiform mole cDNA demonstrates that PSG1-I is a functional type II PSG gene. Using transient expression assays, we demonstrated that the -834/-34 region upstream of the translational start site of the PSG1-I gene contained the PSG promoter elements and the -834 to -456 region contained negative control elements. Sodium butyrate, an inducer of PSG synthesis, greatly stimulated expression of all PSG1-I-chloramphenicol acetyltransferase (CAT) fusion gene constructs. However, butyrate was at least 2-fold more effective in stimulating CAT activity of fusion genes containing upstream sequences (-834 to -576) than those containing proximal sequences (-456 to -172), suggesting two regions in the PSG1-I gene that mediate the butyrate response.
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PMID:Cloning and expression of genes encoding human pregnancy-specific glycoproteins. 164 21

Butyric acid has many strong effects on gene expression in mammalian and viral systems, as well as in increasing the expression of recombinant DNAs artificially introduced into cultured cells. We screened 14 analogues of butyric acid for their ability to upregulate expression from 3 different recombinant chloramphenicol acetyltransferase expression vectors stably integrated into NIH 3T3 cells that had been transformed by calcium phosphate transfection or electroporation. Butyric acid, 2-bromobutyric acid, 3-bromopropionic acid, 3-mercaptopropionic acid, vinylacetic acid, and butyraldehyde were found to upregulate human immunodeficiency viral long terminal repeat-, SV40 early gene promoter-, and glucocerebrosidase promoter-directed expression of heterologous genes in cultured cells. Three other analogues had lesser effects; and 6 additional analogues had very little, if any, effect.
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PMID:Analogues of butyric acid that increase the expression of transfected DNAs. 848 74

The eosinophil-derived neurotoxin (EDN/RNS2) is a member of the mammalian ribonuclease gene family and is one of four proteins found in the large specific granules of human eosinophilic leukocytes. The gene encoding EDN consists of two exons, including a noncoding exon 1, separated by a single intron from the coding sequence in exon 2. We have identified a functional promoter of the EDN gene and shown that optimal expression depends on interaction between the promoter and one or more sequence elements found in the single intron. Cells of the clone 15 eosinophilic variant of the human promyelocytic HL-60 cell line were transfected with constructs that included the promoter region of the EDN gene alone, promoter with exon 1, and promoter with both exon 1 and the intron positioned 5' to the chloramphenicol acetyltransferase (CAT) reporter gene (constructs referred to as PrCAT, PrExCAT, and PrExIn CAT, respectively). Although reporter gene activity from either PrCAT or PrExCAT was only 2-3 fold higher than baseline (CAT alone), inclusion of the single intron (PrExInCAT) resulted in a 28-fold increase in reporter gene activity in uninduced clone 15 cells, and an 80-fold in activity when clone 15 cells were induced to differentiate toward eosinophils with butyric acid. The intron-mediated enhancer activity was reproduced in other human hematopoietic cell lines (K562, Jurkat, U937, and HL-60), but was not found in human 293 kidney cells, suggesting that the function of the enhancer element(s) may be tissue-specific. A significant portion of the observed enhancer activity resides in the first 60 base pairs the the intron, which includes consensus binding sites for both AP-1, and NF-ATp transcription factors, and a 15-base pair segment that is identical to a sequence found in the promoter of the gene encoding the neutrophil granule protein, lactoferrin. The noncoding exon 1/single intron/coding exon 2 genomic structure is a common feature among the mammalian ribonucleases; this finding suggests the possibility of a conserved mechanism of regulation in this gene family.
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PMID:Enhanced expression of the eosinophil-derived neurotoxin ribonuclease (RNS2) gene requires interaction between the promoter and intron. 864 42

We previously identified a major enhancer of the mouse ferritin H gene (FER-1) that is central to repression of the ferritin H gene by the adenovirus E1A oncogene (Tsuji, Y., Akebi, N., Lam, T. K., Nakabeppu, Y., Torti, S. V., and Torti, F. M. (1995) Mol. Cell. Biol. 15, 5152-5164). To dissect the molecular mechanism of transcriptional regulation of ferritin H, E1A mutants were tested for their ability to repress FER-1 enhancer activity using cotransfection with ferritin H-chloramphenicol acetyltransferase (CAT) reporter constructs. Here we report that p300/CBP transcriptional adaptor proteins are involved in the regulation of ferritin H transcription through the FER-1 enhancer element. Thus, E1A mutants that failed to bind p300/CBP lost the ability to repress FER-1, whereas mutants of E1A that abrogated its interaction with Rb, p107, or p130 were fully functional in transcriptional repression. Transfection with E1A did not affect endogenous p300/CBP levels, suggesting that repression of FER-1 by E1A is not due to repression of p300/CBP synthesis, but to E1A and p300/CBP interaction. In addition, we have demonstrated that transfection of a p300 expression plasmid significantly activated ferritin H-CAT containing the FER-1 enhancer, but had a marginal effect on ferritin H-CAT with FER-1 deleted. Furthermore, both wild-type p300 and a p300 mutant that failed to bind E1A but retained an adaptor function restored FER-1 enhancer activity repressed by E1A. Sodium butyrate, an inhibitor of histone deacetylase, mimicked p300/CBP function in activation of ferritin H-CAT and elevation of endogenous ferritin H mRNA, suggesting that the histone acetyltransferase activity of p300/CBP or its associated proteins may contribute to the activation of ferritin H transcription. Recruitment of these broadly active transcriptional adaptor proteins for ferritin H synthesis may represent an important mechanism by which changes in iron metabolism are coordinated with other cellular responses mediated by p300/CBP.
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PMID:Transcriptional regulation of the mouse ferritin H gene. Involvement of p300/CBP adaptor proteins in FER-1 enhancer activity. 1006 17

The effect of butyric acid, a natural fermentation product of colonic bacterial flora, on hepatitis B surface antigen (HBsAg) expression was investigated in HBsAg-positive PLC/PRF/5 human hepatoma cells. By Northern blot analysis, the levels of HBsAg mRNA increased dose-dependently using sodium butyrate (0-2 mmol/l). In transient chloramphenicol acetyltransferase plasmid transfection experiments, the HBsAg-preS2 promoter activity as well as the HBV enhancer 1 activity was stimulated by sodium butyrate, whereas the HBsAg-preS1 promoter activity was not. These results indicate that butyric acid functions as a physiological regulator of HBsAg expression through the portal blood flow and possibly contributes to increased expression ratio of preS2/S to preS1 polypeptides recognized in persistant HBV infection.
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PMID:Enhanced expression of hepatitis B surface antigen by sodium butyrate in PLC/PRF/5 human hepatoma cells. 2154 13